The goals of our research are to continue our investigations of the behavioral, neurochemical and morphologic consequences of repeated administration of d-methamphetamine. Our efforts are now focused on delineating the mechanisms underlying the d-methamphetamine induced depletion of brain catecholamines and the functional consequences of these changes. Of great importance is our finding that some monkeys show permanent deficits in skilled motor performance which is corrected by the administration of L-DOPA. Further studies of the actions of L-DOPA, physostigmine and atropine in such animals are planned. In addition, we are attempting to determine the relationship between tolerance to certain of the behavioral actions of d-methamphetamine and the depletion of brain catecholamines. Finally, we are determining whether the irreversible changes in brain catecholamines produced by d-methamphetamine is an action shared by other psychomotor stimulant drugs (e.g., methylphenidate). In the past six months we have finally succeeded in developing a dosing regimen of d-methamphetamine in rats and guinea pigs which produces long-lasting changes in brain catecholamines which we have previously observed in rhesus monkeys. This cross-species confirmation of the finding adds considerable weight to its significance for man. On a more practical level, it will allow us to do certain neurochemical, neurophysiological and morphologic studies which would be impractical to carry out in the rheus monkey for reasons of cost.